Endocrine Abstracts

We have used a sensitive chemiluminescence GH assay to analyse 24-hour GH profiles (20 minute sampling) from 11 adult cancer survivors with severe GH deficiency acquired following brain irradiation in childhood for non-pituitary brain tumours and 30 matched healthy normal volunteers. Cluster analysis revealed that the area under the curve for GH (AUC_GH), absolute (maximum) GH peak height, mean peak height, maximum pulse area, mean pulse area, absolute (minimum) nadir, and mean valley nadir levels were significantly reduced (P<0.05) in the patients. Complete separation between GH deficiency and normality was achieved by the absolute GH peak (less than 2 microgram per litre in the patients) and almost completely by the AUC_GH. No difference was observed in the pulse duration, interpulse interval, or pulse frequency. Cosinor analysis showed no difference in the acrophase of the diurnal variation (mean ± SEM, 0224 h ± 26 min in the patients vs. 0216 h ± 33 min in normals) or the relative amplitude. Pulsatile secretion was relatively more attenuated than basal secretion in the patients who had significantly (P<0.0001) lower pulsatile AUC_GH / total AUC_GH ratio (45%) compared with that seen in normals (76%). Approximate entropy (ApEn) scores (mean ± SEM) were significantly (P<0.05) raised in the patients (0.705 ± 0.095) compared with all normals (0.458 ± 0.042).

Radiation inflicts quantitative damage to the h-p axis that leads to amplitude-dependent dampening of GH secretion with relative preservation of non-pulsatile (tonic) secretion. Qualitative perturbation in hypothalamic control of GH release, however, is evident by the increase in ApEn values reflecting more disordered GH secretion. The integrity of the h-p axis and, hence, GH neuroregulation is fundamentally preserved in the irradiated GH-deficient patients with a GH secretory pattern similar to that observed in normals and those with GH deficiency due to other etiologies.